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Context Episodic breathlessness is a distressing and difficult to treat symptom because of its short duration. Fast actioned intranasal fentanyl (INF) is potentially more suitable than oral opioids. Objectives To examine the feasibility, preliminary efficacy, and safety of INF for the treatment of episodic breathlessness from advanced nonmalignant conditions in hospice patients. Methods Phase IIB, double-blind, randomized controlled, multisite, INF citrate solution vs. placebo crossover feasibility study. Opioid-tolerant patients were to treat six episodes of breathlessness using INF spray. The primary outcome was change in the Visual Analogue Scale for dyspnea (VAS-D) score from baseline to 15 minutes after study drug's administration (VAS-D15). Other outcomes were to collect demographic data and determine the use of rescue medications, safety, and feasibility of the study design. Results Twenty-one of 49 eligible patients were enrolled, and 19 (90%) patients completed the study. The mean difference in VAS-D15 between fentanyl and placebo was −3.37 mm (95% CI = −10.35 to 3.61 mm; P = 0.337). There was no statistically significant or clinically meaningful difference between INF and placebo in relieving the sensation of discomfort in episodic breathlessness. No significant drug-related adverse event or detrimental effect on vital signs was observed. Conclusion We found no difference between INF and placebo in relieving episodic breathlessness in nonmalignant conditions. INF was well tolerated, and the study design proved to be feasible in hospice patients with advanced diseases. Future study using higher concentration of fentanyl solution may be warranted.